TY  - JOUR
A1  - Lenz, Dominic
A1  - Pahl, Jens
A1  - Hauck, Fabian
A1  - Alameer, Seham
A1  - Balasubramanian, Meena
A1  - Baric, Ivo
A1  - Boy, Nikolas
A1  - Church, Joseph A.
A1  - Crushell, Ellen
A1  - Dick, Anke
A1  - Distelmaier, Felix
A1  - Gujar, Jidnyasa
A1  - Indolfi, Giuseppe
A1  - Lurz, Eberhard
A1  - Peters, Bianca
A1  - Schwerd, Tobias
A1  - Serranti, Daniele
A1  - Kölker, Stefan
A1  - Klein, Christoph
A1  - Hoffmann, Georg F.
A1  - Prokisch, Holger
A1  - Greil, Johann
A1  - Cerwenka, Adelheid
A1  - Giese, Thomas
A1  - Staufner, Christian
T1  - NBAS Variants Are Associated with Quantitative and Qualitative NK and B Cell Deficiency
T2  - Journal of Clinical Immunology
N2  - Purpose
Biallelic pathogenic NBAS variants manifest as a multisystem disorder with heterogeneous clinical phenotypes such as recurrent acute liver failure, growth retardation, and susceptibility to infections. This study explores how NBAS-associated disease affects cells of the innate and adaptive immune system.

Methods
Clinical and laboratory parameters were combined with functional multi-parametric immunophenotyping methods in fifteen NBAS-deficient patients to discover possible alterations in their immune system.

Results
Our study revealed reduced absolute numbers of mature CD56dim natural killer (NK) cells. Notably, the residual NK cell population in NBAS-deficient patients exerted a lower potential for activation and degranulation in response to K562 target cells, suggesting an NK cell–intrinsic role for NBAS in the release of cytotoxic granules. NBAS-deficient NK cell activation and degranulation was normalized upon pre-activation by IL-2 in vitro, suggesting that functional impairment was reversible. In addition, we observed a reduced number of naïve B cells in the peripheral blood associated with hypogammaglobulinemia.

Conclusion
In summary, we demonstrate that pathogenic biallelic variants in NBAS are associated with dysfunctional NK cells as well as impaired adaptive humoral immunity.
KW  - NBAS
KW  - inborn error of immunity
KW  - NK cell deficiency
KW  - B cell deficiency
KW  - vesicle trafficking
KW  - familial hemophagocytic lymphohistiocytosis
Y1  - 2021
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/30836
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-308362
SN  - 0271-9142
SN  - 1573-2592
VL  - 41
IS  - 8
ER  -